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| 1 | Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210显示文摘Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas(RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response.Methods: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th,2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017.Results: After a median follow-up of 242(range, 29–567) days, RCHs were observed in 85.7%(84/98) of patients on cutaneous/mucosal surfaces; 84.5%(71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort(P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9%(24/83). However, no responders were observed among the patients without RCHs.Conclusions: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events. | Xuelian Chen Lanying Ma Xi Wang Hongnan Mo Dawei Wu Bo Lan Dong Qu Hongtu Zhang Jing Huang Binghe Xu | 2019 | Cancer Biology & Medicine2019，16，1： | 53 |
| 2 | The prognostic and therapeutic implications of circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers in the first-line chemotherapy of HER2-negative metastatic breast cancer显示文摘Background:Epithelial-mesenchymal transition(EMT)is implicated in the metastatic process and presents a chal-lenge to epithelial cell adhesion molecule-based detection of circulating tumor cells(CTCs),which have been demon-strated to be a prognostic indicator in metastatic breast cancer.Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression,no standard recommendations have been established for clinical practice.This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients.Methods:We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes(including epithelial CTCs,biphenotypic epithelial/mesenchymal CTCs,and mesenchymal CTCs)in peripheral blood samples.Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival(PFS)rate were conducted to determine the optimal cut-off values,and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination.Results:For predicting the 1-year PFS rate,the optimal cut-off value of total CTC count was 9.5(Area under the curve[AUC]=0.538,95%confidence interval[CI]=0.418-0.657),and that of the proportion of mesenchymal CTCs was 10.7%(AUC=0.581,95%CI=0.463-0.699).We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%.Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria(6.2 vs.9.9 months,P=0.010).A nomogram was constructed based on the criteria and significant clinicopatho-logical characteristics with a C-index of 0.613(P=0.010).Conclusions: The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer. | Xiuwen Guan Fei Ma Chunxiao Li Shiyang Wu Shangying Hu Jiefen Huang Xiaoying Sun Jiayu Wang Yang Luo Ruigang Cai Ying Fan Qiao Li Shanshan Chen Pin Zhang Qing Li Binghe Xu | 2019 | Cancer Communications2019，39，1： | 15 |
| 3 | Application of next-generation sequencing technology to precision medicine in cancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology显示文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation. | Xuchao Zhang Zhiyong Liang Shengyue Wang Shun Lu Yong Song Ying Cheng Jianming Ying Weiping Liu Yingyong Hou Yangqiu Li Yi Liu Jun Hou Xiufeng Liu Jianyong Shao Yanhong Tai Zheng Wang Li Fu Hui Li Xiaojun Zhou Hua Bai Mengzhao Wang You Lu Jinji Yang Wenzhao Zhong Qing Zhou Xuening Yang Jie Wang Cheng Huang Xiaoqing Liu Xiaoyan Zhou Shirong Zhang Hongxia Tian Yu Chen Ruibao Ren Ning Liao Chunyan Wu Zhongzheng Zhu Hongming Pan Yanhong Gu Liwei Wang Yunpeng Liu Suzhan Zhang Tianshu Liu Gong Chen Zhimin Shao Binghe Xu Qingyuan Zhang Ruihua Xu Lin Shen Yilong Wu | 2019 | Cancer Biology & Medicine2019，16，1： | 14 |
| 4 | Anlotinib has good efficacy and low toxicity: a phase Ⅱ study of anlotinib in pre-treated HER-2 negative metastatic breast cancer显示文摘Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response. | Nanlin Hu Yiran Si Jian Yue Tingting Sun Xue Wang Zhuqing Jia Songlin Gao Qiao Li Yang Shao Jiayu Wang Yang Luo Fei Ma Binghe Xu Peng Yuan | 2021 | Cancer Biology & Medicine2021，18，3： | 11 |
| 5 | Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer(ESWN 01):a prospective randomized,multicenter,open-labeled phase 3 trial显示文摘Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC. | Jing Huang Binghe Xu Ying Liu Junxing Huang Ping Lu Yi Ba Lin Wu Yuxian Bai Shu Zhang Jifeng Feng Ying Cheng Jie Li Lu Wen Xianglin Yuan Changwu Ma Chunhong Hu Qingxia Fan Xi Wang | 2019 | Cancer Communications2019，39，1： | 8 |
| 6 | Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2(HER2)-positive early-stage breast cancer: A real-world retrospective study in Chinese patients显示文摘Objective: To assess the long-term effectiveness and safety of trastuzumab in adjuvant therapy for Chinese patients with early-stage human epidermal growth factor 2(HER2)-positive breast cancer in a real-world setting.Methods: This retrospective observational study analyzed the medical records of HER2-positive breast cancer patients between 2000 and 2012 at the Chinese Academy of Medical Sciences. Patients who received adjuvant chemotherapy alone or adjuvant chemotherapy followed by/combined with trastuzumab were included. The Kaplan-Meier method was used to estimate disease-free survival(DFS) and overall survival(OS). Hazard ratios(HR) and 95% confidence intervals(95% CI) were calculated using the Cox regression model.Results: Of the 1,348 patients analyzed, 909 received chemotherapy alone and 439 received chemotherapy plus trastuzumab. The 3-year, 5-year and 10-year DFS rates were 83.70%, 76.38% and 68.94%, respectively, in the chemotherapy-alone cohort, and 90.21%, 86.19% and 83.45% in the chemotherapy plus trastuzumab cohort. The3-year, 5-year and 10-year OS rates were 96.10%, 91.40% and 81.88% in the chemotherapy-alone cohort, and98.17%, 94.91% and 90.01% in the chemotherapy plus trastuzumab cohort. The chemotherapy plus trastuzumab group had a significantly lower risk of disease recurrence and death than the chemotherapy-alone group(DFS:HR=0.50, 95% CI, 0.37-0.68;P<0.001;OS: HR=0.53, 95% CI, 0.34-0.81;P=0.004) after adjusting for covariates.In the 439 patients treated with trastuzumab, multivariate analysis suggested that lymph node positivity, higher T stages, and hormone receptor-negative status were significantly associated with higher risks of disease recurrence,and lymph node positivity and hormone receptor-negative status were significantly associated with higher risks of death. Grade 3/4 adverse events(incidence ≥1%) were more common in patients receiving trastuzumab(54.44% vs.15.73%).Conclusions: Early-stage HER2-positive breast cancer patients treated with trastuzumab plus adjuvant chemotherapy have a significant survival benefit compared with chemotherapy-alone in real-world settings. Lymph node positivity, hormone receptor-negative status, and higher T stages may be associated with higher risks of recurrence, and effective therapy for patients with these factors is required. | Jihong Guo Qing Li Pin Zhang Peng Yuan Jiayu Wang Fei Ma Ying Fan Ruigang Cai Yang Luo Qiao Li Binghe Xu | 2019 | Chinese Journal of Cancer Research2019，31，5： | 6 |
| 7 | Clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA from breast cancer patients in China显示文摘Background:TP53 mutations are common in breast cancer.There is currently no large-scale cohort study to investigate the TP53 landscape in breast cancer patients from China.The predictive value of TP53 mutations for the efficacy of human epidermal growth factor receptor 2(HER2)-targeted therapy in breast cancer remains controversial.In the present study,we aimed to analyze the clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA(ctDNA)from breast cancer patients in China.Methods:We retrospectively analyzed the clinical data and TP53 mutation features in ctDNA samples from 804 patients withmetastatic breast cancer.TP53 mutations were detected by target region capture-based next-generation sequencing.The relationship between TP53 mutation status and disease-free survival(DFS)was analyzed in 444 patientswithmetastatic breast cancer.Moreover,the relationship between TP53 mutation status and progression-free survival(PFS)was analyzed in 55 HER2-positive patients treated with first-line trastuzumab-based therapy.Kaplan-Meier analysis was performed to estimate the survival curves of the different subgroups,and the log-rank test was used to compare the curves.A Cox regression model was used to estimate multivariable-adjusted hazard ratios and their 95%confidence intervals(CIs)associated with the DFS and PFS.Results:Among the 804 investigated patients,431(53.6%)patients harbored TP53 mutations.TP53 mutations were differentially distributed among different molecular subtypes of breast cancer(P<0.05).Patients with TP53 mutations had a shorter DFS than those with wild-type TP53(hazard ratio=1.32,95%CI=1.09-1.61,P=0.005).TP53 mutations in exons 5-8 were associated with worse outcome(hazard ratio=1.50,95%CI=1.11-2.03,P=0.009).However,TP53 mutation status was not significantly associated with PFS in HER2-positive patients who received firstline trastuzumab-based therapy(P=0.966).Interestingly,in the taxane combination group,patients with TP53 mutations exhibited longer PFS than those without TP53 mutations(hazard ratio=0.08,95%CI=0.02-0.30,P<0.001).However,in the nontaxane combination group,patients with TP53 mutations displayed shorter PFS than those with wild-type TP53(hazard ratio=4.84,95%CI=1.60-14.66,P=0.005).Conclusions:TP53 mutations in exons 5-8 may be an independent prognostic marker for short DFS in patients with metastatic breast cancer.TP53 mutations had opposite effects on trastuzumab-treated patients treated with and without taxanes. | Zongbi Yi Fei Ma Guohua Rong Yanfang Guan Chunxiao Li Binghe Xu | 2020 | Cancer Communications2020，40，6： | 5 |
| 8 | Treatment patterns for adjuvant docetaxel-based chemotherapy in early-stage breast cancer in China:A pooled retrospective analysis of four observational studies显示文摘Objective:Adjuvant docetaxel-based chemotherapy is frequently used for operable early breast cancer(EBC).This study investigated patterns of use of docetaxel(T)in real-life clinical practice in China.Methods:This was a retrospective pooled analysis of the Asia-Pacific Breast Initiatives(APBI)Ⅰ(2006–2008)and Ⅱ(2009–2011)registries,and two Chinese observational studies;BC STATE(2011–2014)and BC Local Registry(2007–2010).Female Chinese adults(≥18 years)with operable breast cancer treated with docetaxel-based adjuvant chemotherapy were included in the analysis.Patients with metastatic disease were excluded.The primary endpoint was assessment of treatment patterns and patient profiles.A logistic regression analysis was conducted to identify factors associated with choice of adjuvant chemotherapy regimen.Results:Data from 3,020 patients were included.The most frequently used adjuvant regimen was docetaxel/anthracycline combination[n=1,421(47.1%);of whom 52.0%received T/epirubicin(E)/cyclophosphamide(C)],followed by docetaxel/other[n=705(23.3%);of whom 72.8%received TC],docetaxel/anthracycline sequential[n=447(14.8%);of whom 40.9%and 39.6%received 5-Fu/EC-T and EC-T,respectively],and'other'[n=447(14.8%);of whom 91.5%received T].A significant association was found between adjuvant therapy with docetaxel/anthracycline combination and patient weight,menopausal status and estrogen receptor status.Conclusions:Real-world data revealed that docetaxel/anthracycline combination is the most commonly used category of docetaxel-based adjuvant therapy for patients with operable breast cancer in China;of which TEC is the most frequently used regimen. | Binghe Xu Zhimin Shao Shui Wang Zefei Jiang Xichun Hu Xiaohua Zhang Xiru Li Jinping Liu Mengquan Li Shu Wang | 2018 | Chinese Journal of Cancer Research2018，30，3： | 5 |
| 9 | Efficacy and safety of duloxetine in Chinese breast cancer patients with paclitaxel-induced peripheral neuropathy显示文摘Objective: Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy(PIPN) in Chinese breast cancer patients.Methods:A total of 102 patients with a median age of 50(range,25–60)years,treated in the Department of Medical Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between November 2014 and January 2017 were finally enrolled.Stratified by baseline characteristics,the patients were classified into two groups,receiving either duloxetine or alternative antineurotoxicity drugs.During the course of the paclitaxel regimen,the eligibility criteria included sensory neuropathy,as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events.The treatment consisted of receiving 30 mg duloxetine(for the first 4 weeks)and 60 mg duloxetine for an additional 8 weeks,or any other anti-neurotoxicity drug daily during the same crossover period.The improvement associated with PIPN from the patient’s perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane(FACT-Tax)Scales,which contained questions scored from 0 to 4(0,not at all;4,very much;total score range,0–44).Results:Duloxetine was more effective in decreasing PIPN(odds ratio=5.426;95%confidence interval,1.898–15.514;P=0.002).Between duloxetine group and control group,the median(25th–75th percentiles)decreasing difference in the FACT-Tax pain score was 4(2–6)vs.1(0–4)(P=0.005).Conclusions:Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with PIPN.Non-neuropathy adverse events were mild and similar in both groups.The major toxicities of duloxetine included nausea,constipation,somnolence,dizziness and distention of the eyes.Further examination of the benefits of duloxetine in the prevention of PIPN is required. | Jiani Wang Qing Li Binghe Xu Tongtong Zhang Shanshan Chen Yang Luo | 2017 | Chinese Journal of Cancer Research2017，29，5： | 5 |
| 10 | Validity of distress thermometer for screening of anxiety and depression in family caregivers of Chinese breast cancer patients receiving postoperative chemotherapy显示文摘Objective:Family caregivers(FCs)of breast cancer patients play a vital role throughout the treatment process.Psychological distress of FCs is common and often ignored.A simple and effective instrument for screening psychological distress would help in selecting those FCs requiring special attention and intervention.Here,the validity of distress thermometer(DT)in FCs of Chinese breast cancer patients receiving postoperative chemotherapy was assessed,and the prevalence of anxiety and depression was evaluated.Methods:We recruited 200 FCs of hospitalized breast cancer patients in this cross-sectional descriptive study.Before the first cycle of adjuvant chemotherapy,the levels of anxiety and depression among FCs were assessed using DT and Hospital Anxiety and Depression Scale(HADS).In total,191 valid cases were analyzed.HADS was used as the diagnostic standard to assess the effectiveness of DT as a screening tool for anxiety and depression as well as to analyze the diagnostic efficiency of DT at various cutoff points.Results:The definitive prevalence of both anxiety and depression was 8.90%.The mean level of anxiety and depression among FCs was 5.64±3.69 and 5.09±3.85,respectively,both of which were significantly higher than corresponding Chinese norms(P<0.01).The areas under receiver operating characteristic curves of DT for the diagnoses of FCs'anxiety and depression were 0.904 and 0.885,respectively.A cutoff value of 5 produced the best diagnostic effects of DT for anxiety and depression.Conclusions:The levels of both anxiety and depression were higher in the FCs of Chinese breast cancer patients receiving postoperative chemotherapy than the national norm.DT might be an effective tool to initially screen psychological distress among FCs.This process could be integrated into the palliative care of breast cancer patients and warrant further research. | Min Yang Fei Ma Bo Lan Jianqiang Cai Xiaoying Sun Binghe Xu | 2020 | Chinese Journal of Cancer Research2020，32，4： | 5 |
| 11 | Neuroendocrine carcinoma of the breast:a review of 126 cases in China显示文摘Neuroendocrine carcinoma of the breast (NECB) accounts for approximately 0.3%-0.5% of all breast cancers [1, 2]. Due to the rarity of NECB, current understanding of this disease in China is limited to case reports and small case series, and large data analysis is still lacking. Therefore, we conducted the most comprehensive literature search to date, aiming to analyze the clinicopathologic characteristics as well as treatment and outcome of NECB in the Chinese population. | Yiqun Li Feng Du Wenjie Zhu Binghe Xu | 2017 | Chinese Journal of Cancer2017，36，9： | 5 |
| 12 | The association between early-onset cardiac events caused by neoadjuvant or adjuvant chemotherapy in triple-negative breast cancer patients and some novel autophagy-related polymorphisms in their genomic DNA: a real-world study显示文摘Background:An increasing number of cancer patients die of cardiovascular diseases.The cardiotoxicity of chemo-therapy is particularly important in triple-negative breast cancer(TNBC)with limited therapeutic options.Cardiac autophagy is an important mechanism of cardiotoxicity.This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC,screen the susceptible population,and determine the relationship between cardiotoxicity and autophagy-related polymorphisms.Methods:From a total of 2450 stage I-III TNBC patients,147 met the inclusion criteria and finally recruited.Electro-cardiography(ECG)was performed before most chemotherapy cycles,and echocardiography(UCG)was performed according to clinical needs.All ECG and UCG records were re-interpreted by cardiologists at the National Center for Cardiovascular Disease,Fuwai Hospital.According to the National Center for Biotechnology Information and the Catalog of Somatic Mutations in Cancer database,we selected 25 single nucleotide polymorphisms(SNPs)related to autophagy and genotyped the 147 TNBC patients.Paired-sample T tests,Chi squared tests,and logistic regression models were employed for the analysis.Results:Only 46(31.3%)patients had normal ECG records after every chemotherapy cycle.Among the 16 patients who underwent UCG,2(12.5%)had a reversible decrease of left ventricular ejection fraction.The use of anthracyclines and excessive alcohol consumption were risk factors of ECG abnormalities.With the continuation of chemotherapy,heart rate gradually increased.Anthracyclines were associated with QRS duration abnormalities(P=0.043).After genotyping for 25 autophagy-related SNPs,we found that the G allele of autophagy-related 13(ATG13)rs10838611 was significantly associated with ECG abnormalities(odds ratio=2.258,95%confidence interval=1.318-3.869;P=0.003).Conclusion:ECG abnormalities caused by chemotherapy are common in the real world.Autophagy-related SNPs are associated with chemotherapy-induced cardiotoxicity,thereby providing new evidence for autophagy as a cause of chemotherapy-induced cardiac damage. | Binliang Liu Tao An Meiying Li Zongbi Yi Chunxiao Li Xiaoying Sun Xiuwen Guan Lixi Li Yanfeng Wang Yuhui Zhang Binghe Xu Fei Ma Yixin Zeng | 2018 | Cancer Communications2018，38，1： | 5 |
| 13 | Targeted therapeutic options and future perspectives for HER2-positive breast cancer显示文摘Over the past 2 decades,there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2(HER2)-positive breast cancer.Trastuzumab,pertuzumab,lapatinib,and ado-trastuzumab emtansine(T-DM1)are commonly recommended anti-HER2 target agents by the U.S.Food and Drug Administration.This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices.In this article,we present the data on anti-HER2 clinical research of neoadjuvant,adjuvant,and metastatic studies from the past 2 decades.We also highlight some of the promising strategies that should be critically considered.Lastly,this review lists some of the ongoing clinical trials,findings of which may soon be available. | Jiani Wang Binghe Xu | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 5 |
| 14 | Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA显示文摘Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS. | Anjie Zhu Peng Yuan Nanlin Hu Mingzhou Li Wenmiao Wang Xue Wang Jian Yue Jiayu Wang Yang Luo Fei Ma Pin Zhang Qing Li Binghe Xu Shanbo Cao Giuseppe Lippi Yoichi Naito Mohammed A.Osman Gustavo N.Marta Gianluca Franceschini Armando Orlandi | 2021 | Cancer Biology & Medicine2021，18，3： | 4 |
| 15 | Breast cancer:an up-to-date review and future perspectives显示文摘Breast cancer is the most common cancer worldwide.The occurrence of breast cancer is associated with many risk factors,including genetic and hereditary predisposition.Breast cancers are highly heterogeneous.Treatment strategies for breast cancer vary by molecular features,including activation of human epidermal growth factor receptor 2(HER2),hormonal receptors(estrogen receptor[ER]and progesterone receptor[PR]),gene mutations(e.g.,mutations of breast cancer 1/2[BRCA1/2]and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha[PIK3CA])and markers of the immune microenvironment(e.g.,tumor-infiltrating lymphocyte[TIL]and programmed death-ligand 1[PDL1]).Early-stage breast cancer is considered curable,for which local-regional therapies(surgery and radiotherapy)are the cornerstone,with systemic therapy given before or after surgery when necessary.Preoperative or neoadjuvant therapy,including targeted drugs or immune checkpoint inhibitors,has become the standard of care for most early-stage HER2-positive and triple-negative breast cancer,followed by risk-adapted post-surgical strategies.For ER-positive early breast cancer,endocrine therapy for 5-10 years is essential.Advanced breast cancer with distant metastases is currently considered incurable.Systemic therapies in this setting include endocrine therapy with targeted agents,such as CDK4/6 inhibitors and phosphoinositide 3-kinase(PI3K)inhibitors for hormone receptor-positive disease,anti-HER2 targeted therapy for HER2-positive disease,poly(ADP-ribose)polymerase inhibitors for BRCA1/2 mutation carriers and immunotherapy currently for part of triple-negative disease.Innovation technologies of precision medicine may guide individualized treatment escalation or de-escalation in the future.In this review,we summarized the latest scientific information and discussed the future perspectives on breast cancer. | Ruoxi Hong Binghe Xu | 2022 | Cancer Communications2022，42，10： | 4 |
| 16 | Entinostat,a classⅠselective histone deacetylase inhibitor,plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer:A multicenter,randomized,double-blind,placebo-controlled,phase 3 trial显示文摘Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine therapy.Patients were randomized(2:1)to oral exemestane 25 mg/day plus entinostat(n=235)or placebo(n=119)5 mg/week in 28-day cycles.The primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52(range,28—75)years and 222(62.7%)patients were postmenopausal.CDK4/6 inhibitors and fulvestrant were previously used in 23(6.5%)and 92(26.0%)patients,respectively.The baseline characteristics were comparable between the entinostat and placebo groups.The median PFS was 6.32(95%CI,5.30—9.11)and 3.72(95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),respectively.Grade≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 23(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[20(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(ClinicalTrials.gov#NCT03538171). | Binghe Xu Qingyuan Zhang Xichun Hu Qing Li Tao Sun Wei Li Quchang Ouyang Jingfen Wang Zhongsheng Tong Min Yan Huiping Li Xiaohua Zeng Changping Shan Xian Wang Xi Yan Jian Zhang Yue Zhang Jiani Wang Liang Zhang Ying Lin Jifeng Feng Qianjun Chen Jian Huang Lu Zhang Lisong Yang Ying Tian Hongyan Shang | 2023 | Acta Pharmaceutica Sinica B2023，13，5： | 3 |
| 17 | Polymorphisms of MTHFR and TYMS predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer显示文摘Background:Breast cancer is a global problem,and a large number of new cases are diagnosed every year.Capecit-abine is effective in patients with metastatic breast cancer(MBC).Hand-foot syndrome(HFS)is a common adverse effect of capecitabine.In this study,we investigated the association between single nucleotide polymorphisms(SNPs)in genes involved in capecitabine metabolism pathways and capecitabine-induced HFS in Chinese patients with MBC to identify some predictive genetic biomarkers.Methods:We selected 3 genes involved in capecitabine metabolism and screened genetic variants in these target genes.We genotyped a total of 22 SNPs in the thymidylate synthase gene(TYMS),the methylene tetrahydrofolate reductase gene(MTHFR),and the ribonucleotide reductase M1 gene(RRM1)in 342 MBC patients treated with capecit-abine-based chemotherapy.The genotype distributions of each SNP in patients with and without HFS were assessed using Pearson’sχ^(2)test,and the relationship between HFS and genotypes of SNPs was determined using logistic regression analysis.The association between SNPs and their corresponding gene expression was analyzed using the Blood expression quantitative trait loci(eQTL)browser online tools.Results:We found 4 positive sites for HFS in the TYMS and MTHFR genes:TYMS rs2606241(P=0.022),TYMS rs2853741(P=0.019),MTHFR rs3737964(P=0.029),and MTHFR rs4846048(P=0.030).Logistic regression analyses showed that the genotype AG of MTHFR rs3737964[odds ratio(OR)=0.54,95%confidence interval(CI)0.31-0.97,P=0.038]and MTHFR rs4846048(OR=0.54,95%CI 0.30-0.98,P=0.042)were protective factors of HFS,whereas the genotype CT of TYMS rs2853741(OR=2.25,95%CI 1.31-3.87,P=0.012)increased the risk of HFS.The association between the genotype GT of TYMS rs2606241(OR=1.27,95%CI 0.73-2.23,P=0.012)and HFS was uncertain.Further eQTL analyses confirmed that the alleles of rs3737964 and rs4846048 affected the gene expression levels of MTHFR in cis.Conclusions:We have identified four potentially useful pharmacogenetic markers,TYMS rs2606241,TYMS rs2853741,MTHFR rs3737964,and MTHFR rs4846048 to predict capecitabine-induced HFS in MBC patients. | Shaoyan Lin Jian Yue Xiuwen Guan Peng Yuan Jiayu Wang Yang Luo Ying Fan Ruigang Cai Qiao Li Shanshan Chen Pin Zhang Qing Li Fei Ma Binghe Xu | 2019 | Cancer Communications2019，39，1： | 3 |
| 18 | Extracellular matrix-derived mechanical force governs breast cancer cell stemness and quiescence transition through integrin-DDR signaling显示文摘The extracellular matrix(ECM)serves as signals that regulate specific cell states in tumor tissues.Increasing evidence suggests that extracellular biomechanical force signals are critical in tumor progression.In this study,we aimed to explore the influence of ECM-derived biomechanical force on breast cancer cell status.Experiments were conducted using 3D collagen,fibrinogen. | Cong Li Shi Qiu Xiaohan Liu Fengzhu Guo Jingtong Zhai Zhijun Li Linghui Deng Liming Ge Haili Qian Lu Yang Binghe Xu | 2023 | Signal Transduction and Targeted Therapy2023，8，7： | 2 |
| 19 | Current management of chemotherapy-induced neutropenia in adults:key points and new challenges显示文摘Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN. | Committee of Neoplastic Supportive-Care(CONS),China Anti-Cancer Association Committee of Clinical Chemotherapy,China Anti-Cancer Association Yi Ba Yuankai Shi Wenqi Jiang Jifeng Feng Ying Cheng Li Xiao Qingyuan Zhang Wensheng Qiu Binghe Xu Ruihua Xu Bo Shen Zhiguo Luo Xiaodong Xie Jianhua Chang Mengzhao Wang Yufu Li Yuerong Shuang Zuoxing Niu Bo Liu Jun Zhang Li Zhang Herui Yao Conghua Xie Huiqiang Huang Wangjun Liao Gongyan Chen Xiaotian Zhang Hanxiang An Yanhong Deng Ping Gong Jianping Xiong Qinghua Yao Xin An Cheng Chen Yanxia Shi Jialei Wang Xiaohua Wang Zhiqiang Wang Puyuan Xing Sheng Yang Chenfei Zhou | 2020 | Cancer Biology & Medicine2020，17，4： | 2 |
| 20 | Mutational characteristics determined using circulating tumor DNA analysis in triple-negative breast cancer patients with distant metastasis显示文摘Dear editor,Breast cancer has been considered as the most common malignancy and the leading cause of death in women worldwide[1].Triple-negative breast cancer(TNBC)accounts for 10%-20%of breast cancers,which are characterized by the absence of estrogen receptor(ER),progesterone receptor(PR),and amplification of human epidermal growth factor receptor 2(HER2)[2].TNBC is well known for its rapid progressiveness,high rate of distant organ recurrence,and poor prognosis.Metastasis remains the major cause of death for patients with TNBCs.Up to date,the only direct treatment for metastatic TNBCs is chemotherapy,which has been challenged by tumor heterogeneity and drug resistance.Lack of effective targeted therapy for metastatic TNBCs impels researchers to focus on discovering potentially actionable targets through mutational profiling. | Guohua Rong Zongbi Yi Fei Ma Yanfang Guan Yaping Xu Lifeng Li Binghe Xu | 2020 | Cancer Communications2020，40，12： | 2 |
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